Equine herpesvirus has been adapted to tisse culture (in vitro) and to the Syrian hamster (in vivo). In the hamster, infection results in rapidly lethal hepatitis and marked viremia, up to 10" particles/ml of blood. The growth curves (in vitro and in vivo) are practically identical and permit the two systems to be compared in a unique way. Purified virions and sub-viral particles will be analyzed by polyacrylamide gel electrophoresis to determine the structural proteins, lipoproteins and glycoprotein composition. Capsid species isolated from the nucleus will be analyzed and their role in virion maturation will be examined. Viral particles assembled in tissue culture in presence of FUdR are noninfectious and have incomplete nucleoids and they will be characterized as above. In particular the amount, size, and physical characteristics of viral DNA will be examined by standard techniques. The transcription of the viral genome will be investigated by a variety of hybridization techniques. The processing of viral RNA is amenable to analysis and the Poly A content of the transcripts will be determined. The effect of inhibitors of DNA and protein syntheses on the regulation of transcription (abundancy control of transcripts) will be ascertained. The mechanism of resistance of viral replication to hydroxyurea will be studied and the possible role of altered ribonucleotide reductase activities during infection will be examined. Infected isolated nuclei will be employed to investigate RNA and DNA syntheses, and the purification and characterization of a salt-dependent DNA polymerase induced during infection will be carried out. Defective interfering (DI) particles in the in vivo infection will be analyzed for structural proteins and genetic complexity. Studies on the mechanism of interference will be conducted.